This invention relates to novel bis[bis (diphenylphosphino)hydrocarbon]-, bis[bis(diethylphosphino)hydrocarbon]-, bis[diphenylphosphino-diethylphosphino)hydrocarbon]gold(I), silver(I) or copper(I) complexes or tris[bis(diphenylphosphino)ethane]dicopper (I) derivatives which have tumor cell growth-inhibiting activity, novel pharmaceutical compositions containing tumor cell growth-inhibiting amounts of such complexes, and a method for treating tumor cells sensitive to such complexes by administering tumor cell growth-inhibiting amounts of such complexes to a host animal afflicted by such tumor cells. As disclosed more fully below, the active ingredients are cytotoxic to mammalian cells in vitro, for example B16 melanoma cells, and tumoricidal against animal tumor cells in vivo, for example P388 leukemia and M5076 reticulum cell sarcoma in mice.
Dines, Inorg. Chem., 11(12), 2949-52 (1972), discloses bis[1,2-bis(diphenylphosphino)ethane]copper(I) trifluoroacetate. Cariati et al., Inorg. Chim. Acta, 1(2), 315-18 (1967) disclose bis[1,2-bis(diphenylphosphino)ethane]gold(I) chloride. Bates et al., Inorg. Chim. Acta, 81(2), 151-156 (1984) disclose the crystal and molecular structure of bis[1,2-bis(diphenylphosphino)ethane]gold(I) chloride. Sadler et al., J. Chem. Soc., Dalton Trans., 969-974 (1984), discloses the X-ray crystal structure of bis[1,2-bis(diphenylphosphino)ethane]gold(I) hexafluoroantimonate-acetone solvate. Cariati et al., Chim. Ind. (Milan), 52(10, 995-998 (1970), disclose bis[1,2-bis(diphenylphosphino)ethane]gold(I) thiocyanate. Kuhn et al., Chemiker-Zeitung, 105(3), 87-88 (1981), discloses bis[1,2-bis(diphenylphosphino)ethane]silver(I) methanesulfonate. Carty et al., Can. J. Chem., 49, 761-6 (1971), disclose bis[1,2-bis(diphenylphosphino)ethane]copper(I) nitrate. Leoni et al., J.C.S. Chem. Comm., 5, 240-241 (1983 ), disclose bis[1,2-bis(diphenylphosphino)ethane]copper(I) di[copper(mesityl)]. Marsich, et al., J. Inorg. Nucl. Chem., 34(3), 933-46 (1972), disclose dichlorotris-[1,2-bis(diphenylphosphino)ethane]dicopper (I)-bis-chloroform and its bromo and iodo analogs. Albano, J. Chem. Soc., Dalton Trans, 1938-43 (1972), discloses dichlorotris-[1,2-bis(diphenylphosphino)ethane]dicopper(I) bis-acetone. Edwards et al., J. Chem. Soc., Dalton Trans, 637-43 (1975), disclose bis(acetato)tris[1,2-bis(diphenylphosphino)ethane]dicopper(I). Carty et al., Can. J. Chem., 49(5), 761-6 (1971), disclose bis(nitrato) tris[1,2-bis(diphenylphosphino)ethane]dicopper(I). Struck et al., J. Med. Chem., 9, 414-416 (1966), disclose cytotoxic activity for 1,2-bis(diphenyl- phosphino)ethane which is used as a starting material to prepare some of the active ingredients of the pharmaceutical compositions and methods of treatment of the subject invention. None of the aforementioned references disclose or suggest the pharmaceutical compositions or methods of treatment of the instant invention.